DESCRIPTION:The overall objective of this proposal is to deliver true simultaneous radiation and hyperthermia treatments safely and with tumor thermal doses consistent with heat induced radiosensitization. There are three major components to this project: 1) Simultaneous superficial thermoradiotherapy clinical trials that seek to optimize thermal dose delivery and determine normal tissue tolerance; 2) Hyperthermia technology R&D; and 3) In vitro cell studies to define thermal dose objectives for the clinic. This proposal is for a new clinical trial that will evaluate the long-term normal tissue effects and local control of simultaneous thermal and radiotherapy vs. radiotherapy alone in curable but high risk patients with breast carcinoma. Hypotheses are: 1) It is possible to achieve minimum tumor thermal doses (equivalent times at 41C >60 minutes) in the clinic that are compatible with heat induced radiosensitization in vitro when radiation and hyperthermia are delivered simultaneously. Moreover, the overall minimum tumor thermal dose is improved with increasing number of hyperthermia sessions. 2) The thermal enhancement of subacute and late radiation injury from these thermal doses is tolerable and its thermal dose dependence can be characterized. 3) A minimum improvement of 10 to 15 percent in local control within the heated portion of the chest wall will be detected. Specific Aim: In a population of patients with no prior radiotherapy and minimal disease volume but high risk breast cancer, the aplicants will conduct a prospective clinical trial comparing skin and soft tissue changes between heated and non-heated portions of the chest wall (each patient is her own control) to determine the impact of superficial simultaneous hyperthermia and radiation on late radiation effects and local control. The radiotherapy will be conventionally fractionated and will include conventional boosts. The number of hyperthermia treatments will be four in the first arm of this study and will be escalated to eight in the second arm. The hyperthermia field size will be the maximum obtainable (12 cm x 12 cm) and will be directed to the medial or lateral portion of the chest wall (site selected by randomization). Skin/subcutaneous tissue changes will be graded according to the RTOG Late Effects of Normal Tissue (LENT) scale and contracture of skin will be measured by following reference tattoos in the heated and non-heated portions of the chest wall. The main potential benefit to patients is a greater likelihood of local control within the treated volume with tolerable long-term tissue effects. This benefit outweighs the potential risks from the therapy. This study may have a significant beneficial impact for patients with residual high-risk breast carcinoma.